What are the 3 functions of the innate immune system?
Physical/chemical barriers, cellular responses, activation of adaptive immunity
Why is MHC necessary?
T cells can’t recognize free antigen → need MHC to present peptide→ enables T cell activation
Similarities between BCR and TCR?
Both are antigen-specific and generated by gene rearrangement
Differences between BCR and TCR?
BCR binds free antigen (no MHC); TCR requires processed antigen + MHC
What is self-MHC restriction?
T cells only recognize antigen on self-MHC
Where are MHC molecules expressed?
Most cells (Class I), APCs (Class II)
Where are TCRs expressed?
Only on T cells
Components of MHC Class I?
α chain + β2-microglobulin
Components of MHC Class II?
α chain + β chain
Similarity between Class I & II?
Both have peptide-binding groove and present antigens to T cells
Key difference between Class 1 and 2?
Class 1 = 1 chain + β2m; Class 2 = 2 chains
Where is MHC Class I found?
All nucleated cells
Where is MHC Class II found?
APCs (Dendritic cells, macrophages, B cells)
What is the binding groove?
Site where peptide binds on MHC
Why is the binding groove important?
Determines which peptides can be presented
Steps of antigen presentation?
Breakdown → load on MHC → move to surface → T cell recognition
What is the central dogma?
DNA → RNA → Protein
What is an Allele?
Different versions of a gene
What is an Allotype?
Protein product of allele
What is a SNP?
a polymorphism of a single nucleotide (not quite same as mutation)
What is Co-dominance?
Both alleles expressed equally
What is a Haplotype?
Linked genes inherited together
What is a Syngeneic Haplotype?
Genetically identical
What is Congenic Haplotype?
Identical except one locus
What is Polygeny?
Multiple genes → one protein
What is a Polymorphism?
Many versions of a protein due to multiple alleles
Where are MHC genes located?
Chromosome 6
What is HLA?
Human MHC known as Human Leukocyte Antigen complex
What does Complex I encode?
HLA-A, B, C
What does Complex II encode?
HLA-DP, DQ, DR
What does Complex III encode?
Complement + inflammatory cytokines
Complex I presents to which cells?
CD8 T cells
Complex II presents to which cells?
CD4 T cells
Why is co-dominance important?
Increases antigen presentation diversity
How are MHC genes inherited?
As haplotypes from each parent and expressed co-dominantly
What is MHC diversity?
Many alleles in population
Why is MHC diversity important?
Protects against many pathogens
What is MHC promiscuity?
One MHC binds many peptides
Heterozygote advantage?
More alleles = better protection
Balancing selection?
natural selection that maintains multiple alleles in a population keeping MHC diversity high
Directional selection?
Favors one allele, reducing diversity
What are anchor residues?
Key amino acids that bind MHC
Why are anchor residues important?
to determine which peptides fit in the groove
Anchor residues are more important in which class?
Class I because of more restrictive binding
MHC are related to promiscuity?
They relate to promiscuity because Class 2 have less strict binding making them more promiscuous.
How does MHC activate T cells?
Signal 1 = MHC + peptide → TCR
What else is needed for T cells activation?
Signal 2 (costimulation) + Signal 3 (cytokines)
What are the 3 signals for T cell activation?
MHC + peptide (Signal 1), Costimulation (Signal 2) and Cytokines (Signal 3)